Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol

Harry Yim, Robert Haselbeck, Wei Niu, Catherine Pujol-Baxley, Anthony Burgard, Jeff Boldt, Julia Khandurina, John D. Trawick, Robin E. Osterhout, Rosary Stephen, Jazell Estadilla, Sy Teisan, H. Brett Schreyer, Stefan Andrae, Tae Hoon Yang, Sang Yup Lee, Mark J. Burk, Stephen Van Dien

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622 Scopus citations


1,4-Butanediol (BDO) is an important commodity chemical used to manufacture over 2.5 million tons annually of valuable polymers, and it is currently produced exclusively through feedstocks derived from oil and natural gas. Herein we report what are to our knowledge the first direct biocatalytic routes to BDO from renewable carbohydrate feedstocks, leading to a strain of Escherichia coli capable of producing 18 g l 1 of this highly reduced, non-natural chemical. A pathway-identification algorithm elucidated multiple pathways for the biosynthesis of BDO from common metabolic intermediates. Guided by a genome-scale metabolic model, we engineered the E. coli host to enhance anaerobic operation of the oxidative tricarboxylic acid cycle, thereby generating reducing power to drive the BDO pathway. The organism produced BDO from glucose, xylose, sucrose and biomass-derived mixed sugar streams. This work demonstrates a systems-based metabolic engineering approach to strain design and development that can enable new bioprocesses for commodity chemicals that are not naturally produced by living cells.

Original languageEnglish (US)
Pages (from-to)445-452
Number of pages8
JournalNature Chemical Biology
Issue number7
StatePublished - Jun 2011


ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Yim, H., Haselbeck, R., Niu, W., Pujol-Baxley, C., Burgard, A., Boldt, J., Khandurina, J., Trawick, J. D., Osterhout, R. E., Stephen, R., Estadilla, J., Teisan, S., Schreyer, H. B., Andrae, S., Yang, T. H., Lee, S. Y., Burk, M. J., & Van Dien, S. (2011). Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. Nature Chemical Biology, 7(7), 445-452.